Rapid Development of Improved Data-Dependent Acquisition Strategies.

Tandem mass spectrometry (LC-MS/MS) is widely used to identify unknown ions in untargeted metabolomics. Data-dependent acquisition (DDA) chooses which ions to fragment based upon intensities observed in MS1 survey scans and typically only fragments a small subset of the ions present. Despite this inefficiency, relatively little work has addressed the development of new DDA methods, partly due to the high overhead associated with running the many extracts necessary to optimize approaches in busy MS facilities. In this work, we first provide theoretical results that show how much improvement is possible over current DDA strategies. We then describe an in silico framework for fast and cost-efficient development of new DDA strategies using a previously developed virtual metabolomics mass spectrometer (ViMMS). Additional functionality is added to ViMMS to allow methods to be used both in simulation and on real samples via an Instrument Application Programming Interface (IAPI). We demonstrate this framework through the development and optimization of two new DDA methods that introduce new advanced ion prioritization strategies. Upon application of these developed methods to two complex metabolite mixtures, our results show that they are able to fragment more unique ions than standard DDA strategies.

Strategies to Prevent Cholera Introduction during International Personnel Deployments: A Computational Modeling Analysis Based on the 2010 Haiti Outbreak.

BACKGROUND: Introduction of Vibrio cholerae to Haiti during the deployment of United Nations (UN) peacekeepers in 2010 resulted in one of the largest cholera epidemics of the modern era. Following the outbreak, a UN-commissioned independent panel recommended three pre-deployment intervention strategies to minimize the risk of cholera introduction in future peacekeeping operations: screening for V. cholerae carriage, administering prophylactic antimicrobial chemotherapies, or immunizing with oral cholera vaccines. However, uncertainty regarding the effectiveness of these approaches has forestalled their implementation by the UN. We assessed how the interventions would have impacted the likelihood of the Haiti cholera epidemic. METHODS AND FINDINGS: We developed a stochastic model for cholera importation and transmission, fitted to reported cases during the first weeks of the 2010 outbreak in Haiti. Using this model, we estimated that diagnostic screening reduces the probability of cases occurring by 82% (95% credible interval: 75%, 85%); however, false-positive test outcomes may hamper this approach. Antimicrobial chemoprophylaxis at time of departure and oral cholera vaccination reduce the probability of cases by 50% (41%, 57%) and by up to 61% (58%, 63%), respectively. Chemoprophylaxis beginning 1 wk before departure confers a 91% (78%, 96%) reduction independently, and up to a 98% reduction (94%, 99%) if coupled with vaccination. These results are not sensitive to assumptions about the background cholera incidence rate in the endemic troop-sending country. Further research is needed to (1) validate the sensitivity and specificity of rapid test approaches for detecting asymptomatic carriage, (2) compare prophylactic efficacy across antimicrobial regimens, and (3) quantify the impact of oral cholera vaccine on transmission from asymptomatic carriers. CONCLUSIONS: Screening, chemoprophylaxis, and vaccination are all effective strategies to prevent cholera introduction during large-scale personnel deployments such as that precipitating the 2010 Haiti outbreak. Antimicrobial chemoprophylaxis was estimated to provide the greatest protection at the lowest cost among the approaches recently evaluated by the UN.

Tips from Former Smokers: A Content Analysis of Persuasive Message Features.

Years of research on message design and effects provides insight regarding the most persuasive message appeals. The purpose of this study was to evaluate the content of the messages being presented in the Centers for Disease Control and Prevention's Tips from Former Smokers campaign. A content analysis of persuasive message design features was conducted to critically examine campaign content. Campaign materials were coded for the presence of message variables including emotional appeals, evidence presentation, message framing, attitude functions, and source characteristics. Four independent coders analyzed 122 campaign messages, including video, print, and social media posts. Results from this content analysis indicate that the campaign contained more fear and guilt appeals, than other emotions. Evidence was typically presented in the form of a narrative from sources with firsthand experience. Suggestions for persuasive message design in large-scale public health communication campaigns are discussed.

Sound and Fury--engaging with the politics and the law of sexual rights.

Although past resistance to sexual rights in global debates has often been grounded in claims to culture, nation and religion, opposition voices are now using, rather than rejecting, the frame of international human rights. This Commentary argues that, despite opponents' attempts to defeat sexual rights with other rights claims, a careful understanding of the principles of international human rights and its legal development exposes how the use of rights to oppose sexual rights should, and will ultimately, fail. The Commentary briefly takes up three kinds of "rights" claims made by opponents of sexual rights: limiting rights to protect rights, textual basis, and universality, and explores the rationales and impact of their application to countering sexual rights. Because sexuality and reproduction intersect as well as diverge in the opposition they face, this struggle matters intensely and plays out across advocacy, programmatic and policy worlds. Underpinning this Commentary is the understanding that opposition to sexual and reproductive health rights uses common arguments about rights principles that must be understood in order to be countered.

Sexual rights as human rights: a guide to authoritative sources and principles for applying human rights to sexuality and sexual health.

This Guide seeks to provide insight and resources to actors interested in the development of rights claims around sexuality and sexual health. After engaging with the vexed question of the scope of sexual rights, it explores the rules and principles governing the way in which human rights claims are developed and applied to sexuality and sexual health, and how that development is linked to law and made a matter of state obligation. This understanding is critical to policy and programming in sexual health and rights, as it supports calling on the relevant range of human rights, such as privacy, non-discrimination, health or other universally accepted human rights, as well as demanding the action of states under their international and national law obligations to support sexual health.

Quantifying invasion resistance: the use of recruitment functions to control for propagule pressure.

Invasive species distributions tend to be biased towards some habitats compared to others due to the combined effects of habitat-specific resistance to invasion and non-uniform propagule pressure. These two factors may also interact, with habitat resistance varying as a function of propagule supply rate. Recruitment experiments, in which the number of individuals recruiting into a population is measured under different propagule supply rates, can help us understand these interactions and quantify habitat resistance to invasion while controlling for variation in propagule supply rate. Here, we constructed recruitment functions for the invasive herb Hieracium lepidulum by sowing seeds at five different densities into six different habitat types in New Zealand's Southern Alps repeated over two successive years, and monitored seedling recruitment and survival over a four year period. We fitted recruitment functions that allowed us to estimate the total number of safe sites available for plants to occupy, which we used as a measure of invasion resistance, and tested several hypotheses concerning how invasion resistance differed among habitats and over time. We found significant differences in levels of H. lepidulum recruitment among habitats, which did not match the species' current distribution in the landscape. Local biotic and abiotic characteristics helped explain some of the between-habitat variation, with vascular plant species richness, vascular plant cover, and light availability, all positively correlated with the number of safe sites for recruitment. Resistance also varied over time however, with cohorts sown in successive years showing different levels of recruitment in some habitats but not others. These results show that recruitment functions can be used to quantify habitat resistance to invasion and to identify potential mechanisms of invasion resistance.

Qualified doctor and medical students' use of resources for accessing information: what is used and why?

BACKGROUND: Learning to access information using resources such as books and search engines is an important and fast changing challenge for doctors and medical students. Many resources exist to support evidence-based clinical decision-making, but a wide range of factors influences their use. OBJECTIVE: To explore qualified doctor and medical students' use of resources for accessing information and to determine what is used and why. METHODS: A stratified sample of 46 participants was recruited in Devon, UK. Participants kept a self-report diary of resources used over a week. The diaries were then used to stimulate recall within a semi-structured interview. Diary data were collated into tables of resource use. Qualitative data from the interviews were transcribed verbatim and thematically analysed. RESULTS: Many resources were used by participants but typically for a short duration of time. Categories of reasons for accessing resources were 'to check', 'to learn' and 'to demonstrate'. The two main factors influencing choice of information resource were 'ease of access' and 'quality of information'. Students accessed more information, for a longer duration. DISCUSSION & CONCLUSION: Resources must be quick to use, easy to access and tailored to the different purposes that they serve for qualified doctors and medical students.

Formal modeling of robot behavior with learning.

We present formal specification and verification of a robot moving in a complex network, using temporal sequence learning to avoid obstacles. Our aim is to demonstrate the benefit of using a formal approach to analyze such a system as a complementary approach to simulation. We first describe a classical closed-loop simulation of the system and compare this approach to one in which the system is analyzed using formal verification. We show that the formal verification has some advantages over classical simulation and finds deficiencies our classical simulation did not identify. Specifically we present a formal specification of the system, defined in the Promela modeling language and show how the associated model is verified using the Spin model checker. We then introduce an abstract model that is suitable for verifying the same properties for any environment with obstacles under a given set of assumptions. We outline how we can prove that our abstraction is sound: any property that holds for the abstracted model will hold in the original (unabstracted) model.

Football (Soccer) as a Probable Cause of Long-Term Neurological Impairment and Neurodegeneration: A Narrative Review of the Debate.

Football (soccer) is the most widely played sport across the globe. Due to some recent high-profile cases and epidemiological studies suggesting football can lead to neurodegeneration, scientific and public interest has been piqued. This has resulted in research into whether an association between football participation and neurodegeneration or neurological impairment is present. It has been theorised that a combination of repeated sub-concussive and concussive injuries, due to ball-heading and head collisions, may lead to neurodegeneration. However, evidence remains conflicting. Due to the popularity of the sport, and the serious conditions it has been linked to, it is important to determine whether repeated head impacts during football participation can play a causative role in neurodegenerative disease. To answer this question, a review of the current literature was carried out. Epidemiological evidence showed a higher incidence of amyotrophic lateral sclerosis amongst amateur and professional footballers and that footballers in positions that involve less contact and heading, e.g., goalkeepers lead significantly longer lives. Additionally, imaging studies reach a similar conclusion, reporting changes in brain structure, blood flow, and inflammatory markers in footballers when compared to controls. However, studies looking at an association between heading frequency and cognition show a lack of consensus on whether a higher heading exposure results in reduced cognition. Similarly, in neuropathological studies, signs of chronic traumatic encephalopathy (CTE) have been found in some former players, with contrasting studies suggesting low levels of CTE-type pathology are found in the general population, regardless of exposure to head trauma. The majority of studies suggest a link between football and neurodegenerative disease. However, the high prevalence of retrospective cohort and cross-sectional studies, often plagued by recall bias, undermine the conclusions drawn. Therefore, until larger prospective cohort studies are conducted, concrete conclusions cannot be made. However, caution can be exercised to limit head impacts.

When principles and pedagogy clash: Moving beyond the limits of scholarly practices in an academic-community partnership with sex worker activists.

While U.S. public health education increasingly promotes community-based participatory research (CBPR) as a mode of socially-responsive research, today's intertwined health and social injustice crises demand honest reckoning with the limitations of CBPR as a framework for change. We are a team of students, fellows, and faculty reflecting on the complexities encountered over three years of collaborative work with street-based sex worker activists, in a city characterised by stark wealth disparities reinforced by policies of the university within which we operate. We centre a peer-based needs assessment survey and report on barriers to resources and services for sex workers to highlight hard choices and often unacknowledged challenges to academic partnerships. Our process intends to unsettle the too-sanguine narratives of CBPR, draw from insights arising in the discipline of law, and illuminate practices needed to honour commitments, translate knowledge to power-shifting action, and constructively engage with those most affected in determining the policies that structure their lives.We ask: Can our privileged position within the academy be usefully analysed, confronted, instrumentalised, and even subverted as we shape new practices and interventions in the name of health justice? How might we imagine principles and practices towards a movement public health?

Sexual and reproductive rights at the United Nations: frustration or fulfilment?

Over the past 20 years, advocates have gained formal recognition for some rights in sexuality and reproduction and established the application of human rights standards to sexual and reproductive health issues more generally. However, careful reflection on the state of norm development across sexuality and reproduction as a field reveals fractures and stagnation in the development of standards, and a lack of synergy among advocates and between frameworks for similar rights. This paper seeks to stimulate a more careful accounting for these realities. It examines the formal processes and rules guiding standard-setting, in light of the different intellectual and ideological genealogies of sexual and reproductive rights. We use (homo)sexual orientation and abortion as case studies of current high-profile human rights standard-setting, with specific attention to the contemporary state of human rights law-making in the United Nations today. By placing these two issues in conjunction, we seek to make visible relationships between the vicious political debates in the UN on abortion and sexual orientation, and the multiple and sometimes divergent statements of independent experts and expert bodies in the UN human rights system on these and other sexual and reproductive rights issues. We offer no answers but seek to highlight the need for more investigation and self-reflection by advocates and scholars on how these forces operate and how to work with them.

Health Justice for LGBT Youths: Combining Public Health and Human Rights.

As a socially marginalized group, LGBT youths experience elevated rates of physical and mental health problems that are leading causes of mortality due to a variety of factors. Minority stress theory links exposure to stigma with health outcome disparities. Structural stigma including biased laws, policies, and societal norms predicts approximately 20% of elevated suicidality among LGBT youths. Comprehensive public health efforts to reduce mental health disparities among LGBT youths need to address structural stigma. An interdisciplinary Health Justice approach is described, in which public health evidence is integrated with human rights principles in keeping with the bioethical Justice Imperative. In this approach, epidemiological research is used to inform public health efforts to address health disparities in LGBT youths due to structural stigma in a way that is (1) empirical; (2) aimed at basic goals of reducing morbidity and mortality; (3) applicable to diverse cultural contexts; (4) capable of amending stigma-related power and associated health inequities; and (5) guided by human rights principles. By applying human rights principles to public health needs, this approach will help to achieve health equity for LGBT youths.

Acute medicine journal survey.

A short survey was circulated by email to members of the Society for Acute Medicine receiving the Acute Medicine journal in January 2010. Responses to the questions relating to journal content and layout are summarised in the figures below (Figures 1-5). There were 75 responses in total, representing just over 10% of those surveyed.

Safe sites, seed supply, and the recruitment function in plant populations.

The extent to which plant populations are seed vs. establishment limited can be understood by quantifying the recruitment function, describing the number of seedlings that establish as a function of the number of seeds added. Here, we derive a general equation for the recruitment function based on a mechanistic model describing how the availability of safe sites (sites suitable for germination and establishment) interacts with the number and distribution of seeds added to a plot to determine the number of recruits. The parameters of this recruitment function have a direct biological interpretation that can provide insight into the processes limiting recruitment in plant populations.

Gabapentin toxicity in renal failure: the importance of dose adjustment.

OBJECTIVE: This case report outlines a significant type of morbidity due to continued use of gabapentin during an episode of acute renal failure. Setting. University teaching hospital. DISCUSSION: Gabapentin is widely used in the management of pain. It is entirely excreted through the renal system so this needs to be considered in any patient becoming acutely ill and developing renal failure. We describe a patient who developed significant deterioration in her conscious level due to iatrogenic gabapentin overdose. CONCLUSION: All doctors need to be aware of the need to review the indications for gabapentin use during periods of acute illness, especially with regard to renal impairment. Off-label use should be discouraged.

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study.

In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using a multimedia training video and CD-ROM we developed after a two-step validation process. We hypothesized that use of CD-ROM interactive training will lead to reliable and valid performance of the neurologic examination by both pediatric neurologists and nonpediatric neurologists. All examiners were asked to take one of six interobserver variability tests found on the CD-ROM on two occasions. In the first interobserver variability evaluation, 89% (531 of 594) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the two items that had a 60% correct rate, the correct response rate rose to 93% (114 of 123). In the second interobserver variability evaluation, 88% (493 of 560) of the responses agreed with the gold standard responses. Following annotated feedback to the examiners about the four items that had a 70% correct rate, the correct response rate rose to 96% (104 of 108). Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children. It provides an effective means to evaluate interobserver variability, offers a route for feedback, and creates an opportunity to reevaluate variability, both immediately and at periodic intervals.

Advancing sexual health through human rights: the role of the law.

Since the International Conference on Population and Development, definitions of sexuality and sexual health have been greatly elaborated alongside widely accepted recognition that sexual health requires respect, protection and fulfilment of human rights. Considerable progress has also been made in enacting or changing laws that affect sexuality and sexual health, in line with human rights standards. These measures include legal guarantees against non-discrimination and violence, decriminalisation of consensual sexual conduct and guaranteeing availability, accessibility, acceptability and quality of sexual health information and services to all. Such legal actions have had positive effects on health and specifically on sexual health, particularly for marginalised populations. Yet in all regions of the world, laws still exist which jeopardise health, including sexual health, and violate human rights. In order to ensure accountability for the rights and health of their populations, states have an obligation to bring their laws into line with international, regional and national human rights standards. These rights-based legal guarantees, while insufficient alone, are essential for effective systems of accountability, achieving positive sexual health outcomes and the respect and protection of human rights.